Differential responses of extracellular GABA to intrastriatal perfusions of 3-nitropropionic acid and quinolinic acid in the rat.
Although both quinolinic acid and 3-nitropropionic acid destroy medium sized, GABAergic, spiny projection neurons after direct perfusion of neurotoxin into the rat striatum, changes in extracellular GABA concentration in the striatum within the first 90 min reflect different toxic mechanisms in these two animal models for Huntington's disease. Since quinolinic acid acts as a potent excitotoxin, the early depolarizing response in GABAergic neurons results in an early increase in extracellular GABA activity (peak at 40 min) whereas the more indirect action of 3-nitropropionic acid on mitochondrial energy metabolism results in a delayed increase in extracellular GABA activity (peak at 60 min) with a pattern of gradual increase and decline. The localized delivery of cytotoxin provides an opportunity for kinetic comparisons of direct and indirect cytotoxic mechanisms that can be useful in developing neuroprotective treatment strategies in Huntington's disease.
Reynolds
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Department of Neurology, The Medical College of Wisconsin, Veterans Affairs Medical Center, Milwaukee 53295, USA.
Lin
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Meyer Cameron
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Roerig
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D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000633:toxicity; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D006816:Huntington Disease / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D008928:Mitochondria / Q000187:drug effects; D009498:Neurotoxins / Q000633:toxicity*; D009574:Nitro Compounds; D010477:Perfusion; D011422:Propionates / Q000633:toxicity; D017378:Quinolinic Acid / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D005680:gamma-Aminobutyric Acid; D013385:Succinate Dehydrogenase; D017378:Quinolinic Acid; C015392:3-nitropropionic acid